Immunization with anti-idiotype (Id) antibodies represents a novel new approach to active immunotherapy. Extensive studies in animal tumor models have demonstrated the efficacy of anti-Id vaccines in preventing tumor growth and curing mice with established tumor. We have developed and characterized several murine monoclonal anti-Id antibodies (Ab2) which mimic distinct human tumor-associated antigens (TAA) and can be used as surrogate antigens for triggering active anti-tumor immunity in cancer patients. Encouraging results have been obtained in recent clinical trials. In this article, we will review the existing literature and summarize our own findings showing the potential of this approach for various human cancers. We will also discuss where anti-Id vaccines may perform better than traditional antigen vaccines.
Certain anti-idiotypic antibodies that bind to the antigen-combining sites of antibodies can effectively mimic the three-dimensional structures and functions of the external antigens and can be used as surrogate antigens for active specific immunotherapy. Extensive studies in animal models have demonstrated the efficacy of these vaccines for triggering the immune system to induce specific and protective immunity against bacterial, viral and parasitic infections as well as tumors. Several monoclonal anti-idiotype antibodies that mimic distinct human tumor-associated antigens have been developed and characterized. Encouraging results have been obtained in recent clinical trials using these anti-idiotype antibodies as vaccines. In this article, we will review the current literature and discuss the potential of this novel therapeutic approach for various human cancers.
We conducted a prospective longitudinal study to determine the nature and prevalence of cardiac abnormalities in systemic lupus erythematosus and to study their natural history and relationship with disease activity. Forty consecutive inpatients with systemic lupus erythematosus were studied during their admission and subsequently 6 to 12 months later. On each occasion a clinical cardiovascular examination was carried out, disease activity was scored using the "Lupus Activity Criteria Count" and a Doppler echocardiographic examination was carried out. 72.5% of patients had an abnormal echocardiogram in the first study while 51.7% were abnormal during the follow-up study. Valvar disease occurred in 37.5% of patients. The mitral valve was most commonly affected. Libman-Sacks endocarditis was rare (2.5%). Pericardial effusions were seen in 36.2% of echocardiograms. The majority (76.0%) of these were associated with hypoalbuminaemia. 80.0% of patients had active disease during the first examination and 41.4% at follow-up. There was no correlation between activity of disease and prevalence of cardiac abnormalities at either examination. We conclude that cardiac disease is common in systemic lupus erythematosus. Prevalence of cardiac abnormality did not correlate with disease activity.
We report a significantly increased prevalence of antiribosomal P protein antibodies in Malaysian Chinese patients (38%) with SLE compared to white Caucasian (13%) and Afro-Caribbean (20%) patients. The increased prevalence was not due to a generalized increase in autoantibody production because anti-dsDNA and anti-SSA antibodies were present in comparable frequencies in the three ethnic groups while anti-Sm and anti-SSB antibodies were rarely found in the Malaysian Chinese patients.
In the 1950s, Bickerstaff and Fisher independently described cases with a unique presentation of ophthalmoplegia and ataxia. The neurological features were typically preceded by an antecedent infection and the majority of patients made a spontaneous recovery. In the cases with Bickerstaff brainstem encephalitis, there was associated altered consciousness and in some, hyperreflexia, in support of a central pathology whereas in Fisher syndrome, patients were areflexic in keeping with a peripheral aetiology. However, both authors recognised certain similarities to Guillain-Barré syndrome such as the presence of peripheral neuropathy and cerebrospinal fluid albuminocytological dissociation. The discovery of immunoglobulin G anti-GQ1b antibodies in patients with Fisher syndrome and later in Bickerstaff brainstem encephalitis was crucial in providing the necessary evidence to conclude that both conditions were in fact part of the same spectrum of disease by virtue of their common clinical and immunological profiles. Following this, other neurological presentations that share anti-GQ1b antibodies emerged in the literature. These include acute ophthalmoparesis and acute ataxic neuropathy, which represent the less extensive spectrum of the disease whereas pharyngeal-cervical-brachial weakness and Fisher syndrome overlap with Guillain-Barré syndrome represent the more extensive end of the spectrum. The conditions can be referred to as the 'anti-GQ1b antibody syndrome'. In this review, we look back at the historical descriptions and describe how our understanding of Fisher syndrome and Bickerstaff brainstem encephalitis has evolved from their initial descriptions more than half a century ago.
AIM: The purpose of this study is to compare the prevalence of rheumatoid factor (RF) isotypes and second generation anti-cyclic citrullinated peptides (anti-CCP) in Malaysian rheumatoid arthritis (RA) patients.
METHODS: In this cross-sectional study, 147 established RA patients from three ethnic groups were recruited from a major rheumatology clinic in Malaysia. Enzyme-linked immunosorbent assays (ELISA) for serum RF isotypes IgA, IgG and IgM as well as second-generation anti-CCP were performed and the prevalence of each auto-antibody was compared in the three ethnic groups.
RESULTS: The anti-CCP was the most prevalent auto-antibody in each of the ethnic groups, followed closely by RF IgM and RF IgG. Rheumatoid factor IgA was the least prevalent across all three ethnic groups. The anti-CCP-RF IgM combination provided the best test sensitivity. Seroprevalence of anti-CCP was strongly associated with the presence of each of the RF isotypes. The seroprevalence of RF and anti-CCP did not increase or decrease with advancing age, age at onset and disease duration.
CONCLUSION: When used alone, anti-CCP provides a diagnostic advantage over RF IgM on the basis of test sensitivity. Considering the high cost of the anti-CCP assay, step-wise serum testing with IgM RF followed by anti-CCP may provide a more economically sensible option to optimize test sensitivity for RA.
Study site: Rheumatology clinic, Hospital Tuanku Jaafar, Seremban, Negeri Sembilan, Malaysia
Anti-idiotype (Id) vaccine therapy has been tested and shown to be effective, in several animal models, for triggering the immune system to induce specific and protective immunity against bacterial, viral and parasitic infections. The administration of anti-Id antibodies as surrogate tumor-associated antigens (TAA) also represents another potential application of the concept of the Id network. Limited experience in human trials using anti-Id to stimulate immunity against tumors has shown promising results. In this "counter-point" article, we discuss our own findings showing the potential of anti-Id antibody vaccines to be novel therapeutic approaches to various human cancers and also discuss where anti-Id vaccines may perform better than traditional multiple-epitope antigen vaccines.